The present invention, in some embodiments thereof, relates to a system that determines at least one property of a body tissue by its thermal response during and/or following exposure to ultrasound, and, more particularly, but not exclusively, to a system that distinguishes cancerous from normal tissue using such methods.
A number of medical imaging modalities are used for distinguishing different types of body tissue, and in particular for locating cancer and other diseased tissue, but each of these modalities has some disadvantages. Ultrasound imaging does not distinguish well between some types of soft tissue. X-rays, especially if used for computerized tomography (CT) scans, can distinguish some types of soft tissue, but the resolution and noise level of x-ray images is limited by the harmful effects of too much radiation, and this is especially true of CT images which require much higher x-ray doses than ordinary x-ray images. Magnetic resonance imaging (MRI) is typically better than ultrasound at distinguishing soft tissues, but MRI equipment is generally large and expensive, and often surrounds the patient, providing limited access for performing other procedures in real time. CT equipment, and equipment for nuclear medicine imaging, such as PET, also tends to be large and expensive. Infrared imaging can locate regions on the surface of the body that differ in temperature from surrounding regions, but has limited utility for finding diseased tissue, since the body's temperature control mechanisms tend to make the temperature uniform.
Biopsies are also used for identifying cancer and other diseases, but biopsies are invasive, carrying a risk of infection, and are often uncomfortable for the patient. Furthermore, if a biopsy is done without knowing the location of the suspected diseased tissue, as is normally the case with prostate biopsies, then it may miss the diseased tissue, giving a false negative result.
Ultrasound is used medically both for imaging and for therapy. Ultrasound medical imaging systems generally use short pulses of ultrasound, between 200 and 5000 pulses per second. Safety regulations, for example by the United States Food and Drug Administration (FDA) generally limit ultrasound imaging systems to relatively low time average power, which do not cause the temperature the exposed tissue to increase by more than 3 degrees Celsius. The power within each pulse is generally much greater than average power, to provide adequate signal to noise ratio. For example, FDA regulations limit spatial peak time average power to 720 mW/cm2, but spatial peak pulse average power can be as high as 190 W/cm2. As used herein, “spatial peak time average power” and “spatial peak pulse average power” both refer to the global maximum derated power, as defined in “Information for Manufacturers Seeking Marketing Clearance of Diagnostic Ultrasound Systems and Transducers,” FDA Document 560, issued Sep. 9, 2008.
Ultrasound therapy systems use higher power, and generally increase the temperature of treated tissue by more than 3 degrees Celsius. Some ultrasound therapy systems heat tissue to a much higher temperature over a small volume, in order to ablate it. Ralf Seip et al, “Real-Time Detection of Multiple Lesions During High Intensity Focused Ultrasound (HIFU) Treatments,” presented at International Symposium on Therapeutic Ultrasound, Seattle, 2002, describes an ultrasound therapy system that produces lesions by locally heating tissue to more than 85 degrees C. using 30 to 37 watts total acoustic power, in which the lesions are monitored in real time using scattered ultrasound.
U.S. Pat. No. 7,211,044 to Mast et al describes a therapeutic ultrasound system, in which a low intensity ultrasound signal is first focused on a target tissue, producing a temperature rise of less than 1 degree C. The temperature rise in the target tissue is imaged, to ensure that the ultrasound signal was correctly aimed at the target tissue, and high intensity ultrasound is then focused on the target tissue to administer hyperthermia treatment or to ablate the tissue.
G. E. P. M. Van Venrooij, “Measurement of ultrasound velocity in human tissue,” Ultrasonics, October 1971, p. 240-242, gives data on the sound speed and acoustic impedance for ultrasound in blood, cerebrospinal fluid, and different types of brain tumors. Ferride Severcan, Dana Dorohoi, and Dorina Creanga, “Ultrasound Propagation Through Biological Tissues,” Studia Universitatis Babes-Bolyai, Physica, Special Issue, 2001, p. 169-175, gives the sound speed, acoustic impedance, and absorption coefficient for ultrasound at different frequencies and temperatures in different types of body tissue, and suggests that information about the presence of tumors or foreign bodies can be obtained using physical parameters characterizing ultrasound propagation in tissues.
The online newsletter Bio-Medicine, in an article dated Aug. 17, 2007 and downloaded from <http://www.bio-medicine.org/medicine-technology-1/EDAP-Announces-Launch-of-Clinical-Study-Combining-HIFU-and-Chemotherapy-for-Localized-Aggressive-High-Risk-Prostate-Cancer-4-1/> on Mar. 24, 2009, describes a clinical trial by EDAP TMS S.A. in Lyon, France, a global leader in High Intensity Focused Ultrasound (HIFU) treatment of prostate cancer, in which therapeutic ultrasound is used to ablate stage T2c prostate cancer, in conjunction with chemotherapy agents. The efficacy of the chemotherapy agent in the surrounding tissue is said to be improved by the ultrasound treatment. A synergistic effect of combining ultrasound treatment with chemotherapy in an animal study is reported by Curiel et al, “HIFU and Chemotherapy Synergistic Inhibitory Effect on Dunning AT2 Tumour-Bearing Rats,” 4th International Symposium on Therapeutic Ultrasound, AIP Conference Proceedings, Volume 754, pp. 191-195 (2005).
A. Bounaim et al, “Sensitivity of the ultrasonic CARI technique for breast tumor detection using a FETD scheme,” Ultrasonics 42, 919-925 (2004) describes a simulation of the CARI (clinical amplitude/velocity reconstruction imaging) technique for ultrasound detection of breast cancer, which is said to have “demonstrated clinical potential for improving the differentiation of benign and malignant breast lesions.” The paper cites “clinical studies of the CARI modality [which] have shown that the sound velocity and the acoustic tissue attenuation are important quantitative parameters in characterizing the different tissues of the female breast.”
Bao-wei Dong et al, “In vivo measurements of frequency-dependent attenuation in tumors of the liver,” Journal of Clinical Ultrasound 22, 167-174 (1994), describes measurements of the frequency dependence of ultrasound attenuation in the livers of healthy subjects and subjects with different types of benign and malignant liver tumors. Some of the types of tumors showed higher frequency dependence of attenuation than healthy tissue, while other types of tumors showed lower frequency dependence of attenuation than healthy tissue.
Xiao-Zhou Liu et al, “Ultrasonic characterization of porcine liver tissue at frequency between 25 to 55 MHz,” World J Gastroenterol Apr. 14, 2006; 12(14): 2276-2279, describes greater attenuation of ultrasound found in cirrhotic porcine liver tissue than in normal porcine liver tissue.
L. Landini et al, Medical and Biological Engineering and Computing 24, 243-247 (1986), “reports on measurements of frequency-dependent attenuation of ultrasound in normal and pathological breast tissue . . . including fatty tissue, fibrofatty parenchyma and fibrosis, and malignant tumors with and without productive fibrosis (infiltrating ductal carcinoma scirrhous type and medullary carcinoma, respectively) . . . . The results of the attenuation measurements indicate that the attenuation coefficient is lower for tissues with large predominance of cells (fatty tissue, medullary carcinoma) and increases with collagen fiber content (infiltrating ductal carcinoma scrirrhous type, fibrosis, fibrofatty).”
B. Sfez et al, “Electro-Optical Ultrasound,” Israel Atomic Energy Commission Annual Report, 2001, p. 1-23, downloaded from <http://www.iaec.gov.il/docs/IAEC20.pdf> on Feb. 24, 2009, describes a medical imaging method in which visible or infrared light is transmitted into tissue, and focused ultrasound waves are used to scan the tissue. Although the light is strongly diffused by the tissue, the part of the light that passed through the location where the ultrasound is focused can be identified by its modulation at the ultrasound frequency, and in this way a 3-D map can be reconstructed of the absorption of the light in the tissue.
Victoria S. Hollis, “Non-Invasive Monitoring of Brain Tissue Temperature by Near-Infrared Spectroscopy,” Ph.D. thesis, Dept. of Medical Physics and Bioengineering, University of London, September 2002, in Chapter 4, reviews various methods of measuring brain temperature non-invasively, including near-infrared spectroscopy (NIRS), microwave radiometry, magnetic resonance thermometry, and ultrasound thermometry.
The use of ultrasound to measure tissue temperature non-invasively is also described by W. L. Straube, J. Parry, E. Moros, J. Trobaugh, and R. M. Arthur, in a talk “An In Vivo System for the Determination of the Effect of Temperature on Backscattered Ultrasound Energy in Ultrasonic Images,” presented at 2005 Annual Meeting, Society for Thermal Medicine, Bethesda, Md., Apr. 1-3, 2005, and by R. M. Arthur et al, in a talk “Change in Ultrasonic Backscattered Energy for Temperature Imaging Factors Affecting Temperature Accuracy and Spatial Resolution in 3-D,” presented at the 32nd UITC, Alexandria, Va., May 16, 2007. The authors consider ultrasound backscattering from an inhomogeneous tissue, such as liver tissue with small inclusions of aqueous and lipid material, which have ultrasound backscattering coefficients that have different dependence on temperature. They describe using the resulting spatial variation in backscattering energy to measure the temperature of the tissue.
Seip and Ebbini, “Noninvasive Estimation of Tissue Temperature Response to Heating Fields Using Diagnostic Ultrasound,” IEEE Transactions on Biomedical Engineering, vol 42, pp. 828-839 (1995), describe another technique for using backscattering of diagnostic ultrasound to monitor temperature changes in tissue. The technique is based on the observation that most biological tissues are semi-regular scattering lattices. These lattice structures produce harmonics in the backscattered ultrasound, with the frequency shift of the harmonics depending on temperature, through the temperature dependence of the sound speed, and the thermal expansion of the lattice structure. Autoregressive model-based methods are used to estimate the frequency shift.
Ultrasound has been used for non-destructive testing of a variety of materials, including ceramics, metals, and plastics. Cracks and other defects inside the material may absorb ultrasound more than the bulk material, and are detected by the increased temperature they produce at the surface of the material, which is measured. Typically, the ultrasound transducers produce power densities of more than 100 W/cm2, and are modulated at frequencies ranging from a few Hz down to a few hundredths of a Hz. Examples of such systems are described in Th. Zweschper et al, “Ultrasound excited thermography using frequency modulated elastic waves,” in “Insight,” ISSN 1354-2575, 2003, vol. 45, #3, pp 178-182 (British Institute of Nondestructive Testing); J. Rantala et al, “Lock-in thermography with mechanical loss angle heating at ultrasonic frequencies,” Quantitative Infrared Thermography, Eurotherm Series 50, Edition ETS 1997, pp 389-393; and A. Gleiter et al, “Ultrasound-Lockin-Thermography for Advanced Depth Resolved Defect Selective Imaging,” European Conference on Non-Destructive Testing 2006, paper We.3.8.2, downloaded from <http://www.ndt.net/article/ecndt2006/papers˜1.htm> on Jan. 25, 2009.